Theoretical Prediction of (pKa) and Thermodynamic Parameters Using Dft and PM3 Methods: Application to NSAIDs

Yosef Othman  Homeda; Saif Enad  Ahmed; Idrees Shaban Hassan  Aljubory

doi:10.51699/cajotas.v7i2.1666

Authors

Yosef Othman Homeda Tikrit University, College of Education for Pure Sciences, Department of Chemistry, Iraq
Saif Enad Ahmed Tikrit University, College of Sciences, Department of Chemistry, Iraq
Idrees Shaban Hassan Aljubory Open College of Education, Kirkuk Education Directorate, Iraq

DOI:

https://doi.org/10.51699/cajotas.v7i2.1666

Keywords:

DFT, PM3, pKa, ΔH, ΔG, ΔS, Application, Quantum Calculations

Abstract

In this study, the thermodynamic functions of six pharmaceutical chemical compounds were calculated, and their theoretical ionization constants were determined, including enthalpy change (ΔH), Gibbs free energy change (ΔG), and entropy change (ΔS). These calculations were performed using different theoretical methods, namely the DFT/6-31G method, which is classified as an ab initio computational approach, and the PM3 method, which belongs to the semi-empirical computational methods. A statistical correlation was conducted between the calculated thermodynamic functions (ΔH, ΔG, ΔS) and the experimentally determined ionization constants. The results showed that the DFT/6-31G method yielded the best correlation coefficient between enthalpy values and experimental ionization constants, with a value of R² = 0.9396. Similarly, for the PM3 method, the highest correlation coefficient obtained was R² = 0.9392, also between enthalpy values and experimental ionization constants. An increase in the thermodynamic functions leads to an increase in pKa values, indicating a decrease in acidity, whereas a decrease in the thermodynamic functions results in lower pKa values, corresponding to increased acidity. Hence, the relationship between thermodynamic functions and acidity is inverse.This method is an effective tool for drug and understanding its properties, offering high precision (R² > 0.93).

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